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Biomedical subjects

Margaret F Veale

Publications and source records attributed to Margaret F Veale.

2 recordsLinked to original sources

Red blood cell age determines the impact of storage and leukocyte burden on cell adhesion molecules, glycophorin A and the release of annexin V.

The influence of the age of the red blood cell (RBC) within its 120-day lifecycle at the time of blood donation on the RBC storage lesion is not well understood. Expression of cell adhesion molecules (CAMs) (CD44, CD47, CD58 and CD147), glycophorin A (GPA) and phosphatidylserine (PS) on young and old RBCs density separated prior to storage of the RBC concentrate was determined by flow cytometry. Older RBCs showed significantly reduced expression of GPA throughout storage and CD44 and CD147 from Day 28 onwards compared to young RBCs. Storage in the presence of leukocytes caused a significant decline in the expression of CD44, CD58, CD147 and GPA, whereas RBCs that were pre-storage leukocyte depleted maintained a relatively consistent level of expression throughout storage. PS was not detected at the external RBC membrane of young or old RBCs during storage. Increased levels of annexin V were detected in the supernatant of RBCs stored in the presence of leukocytes, with significantly greater supernatant levels found for old RBCs compared to young RBCs. These findings provide new insight into the RBC storage lesion and indicate that RBC age at the time of donation impacts upon the quality of stored RBC concentrates.

Aging↗

Knockout B lymphoma cell lines as biochemical tools to explore multiple signalling pathways.

Studies on B lymphocyte signalling pathways using B lymphocytes from genetically modified mice have the disadvantages of primary cell polyclonality and finite life span. B lymphoma cell lines have been generated from mice with targeted mutations in the oct-2, OBF-1, vav-1 and btk genes, as a model system that lacks these limitations and possesses additional potential for experimental manipulation. To assess their utility, activation of the B cell receptor using anti- micro, the Toll-like receptor-4 using lipopolysaccharide and the interleukin-4 receptor were assessed in these cell lines. Differential tyrosine phosphorylation of intracellular proteins was measured in the wild-type controls compared to the corresponding mutant cell lines after B cell receptor stimulation. Intracellular calcium (Ca2+i) was mobilized in the control cell lines but not in the OBF-1 and Vav1-deficient cells, while Xid B cell lines (btk mutant) showed a reduced Ca2+ mobilization. Extracellular signal-regulated kinase 1/2 phosphorylation in response to anti- micro or lipopolysaccharide stimulation was significantly reduced in Vav1-deficient cells. Interleukin-4 stimulation of wild-type cells resulted in a 2-3-fold increase in Stat-6 phosphorylation. These results indicate that the cell lines mimic the biochemical responses of the corresponding primary B cells. They therefore represent a useful model system to investigate the regulation and roles of these and other gene products in B cell signal transduction and activation.

Agammaglobulinaemia Tyrosine Kinase↗